Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 39.050
Filtrar
Más filtros

Intervalo de año de publicación
1.
BMC Neurol ; 24(1): 243, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39009960

RESUMEN

Rheumatoid meningitis (RM) is a rare extra-articular manifestation of rheumatoid arthritis (RA) that has been increasingly recognized by neurologists. However, the diversity of its clinical manifestations makes its diagnosis difficult. RM does not have a unified diagnostic standard, and its link with RA needs to be studied further. Here we report two cases of RM without a history of RA. The first patient, an 80-year-old woman, presented with sudden unilateral limb weakness, with brain MR showing abnormal signals in the leptomeningeal of the right frontal parietal. Subarachnoid hemorrhage was excluded after imaging examination, and infectious meningitis was ruled out after cerebrospinal fluid (CSF) examination. The patient was diagnosed as having RM, she had increased levels of CCP and AKA, the markers of RA, but no history of the disease or other clinical manifestations of it. Another case, a 65-year-old man, was hospitalized with Bell's palsy. We found that he had intracranial imaging changes highly consistent with those characteristic of RM during his routine examination. Except for the left peripheral facial palsy, the patient had no other neurological signs or symptoms and no RA history. After a careful physical examination, we found no joint or other manifestations or serological abnormalities consistent with RA (RF, CCP, AKA, etc.). However, after excluding infection meningitis and considering the patient's unique imaging results, we diagnosed him as having RM. We report these two cases as references for clinical diagnosis and treatment of RM, providing a discussion of our rationale.


Asunto(s)
Artritis Reumatoide , Meningitis , Humanos , Femenino , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Anciano de 80 o más Años , Meningitis/diagnóstico , Meningitis/complicaciones , Anciano , Masculino , Imagen por Resonancia Magnética
2.
Int J Rheum Dis ; 27(7): e15199, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39010815

RESUMEN

AIM: To evaluate real-world abatacept retention and clinical outcomes in patients with rheumatoid arthritis in Taiwan. METHODS: This prospective, observational study enrolled patients with rheumatoid arthritis aged ≥20 years who received abatacept in real-world practice. The primary endpoint was the abatacept retention rate at 24 months. Patients were categorized into subgroups based on abatacept treatment status and previous biological disease-modifying antirheumatic drug (bDMARD) therapy. Risk factors affecting abatacept retention were determined by regression analysis. RESULTS: A total of 212 patients were enrolled. The overall abatacept retention rate at 24 months among all patients was 59.9% (95% confidence interval 53.0%-66.6%). Patients who were ongoing users of abatacept and bDMARD-naïve had the highest retention rate (76.3%); of these, 31.6% achieved low disease activity or remission after 2 years. Previous treatment with bDMARDs was associated with an increased risk of abatacept discontinuation (hazard ratio 1.99; p = .002). The most common reasons for abatacept discontinuation were drug switch (11.3%) and loss to follow-up (6.1%). Abatacept was well-tolerated with no new safety signals. CONCLUSION: The 24-month retention rate of abatacept was 59.9%; abatacept was associated with improved clinical outcomes and was well-tolerated in the real-world setting in Taiwan.


Asunto(s)
Abatacept , Antirreumáticos , Artritis Reumatoide , Inducción de Remisión , Humanos , Abatacept/uso terapéutico , Abatacept/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Taiwán/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Resultado del Tratamiento , Estudios Prospectivos , Factores de Tiempo , Anciano , Factores de Riesgo , Adulto , Sustitución de Medicamentos , Cumplimiento de la Medicación
3.
J Ethnopharmacol ; 334: 118566, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002823

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Trifolium alexandrinum L. (TA), has traditionally been used in folk medicine for its anti-inflammatory properties against hyperuricemia and gout. However, the specific mechanisms of action of TA have not been thoroughly studied. AIM OF THE WORK: This study aimed to evaluate the protective effects of irradiated (TR25) and non-irradiated (TR0) Trifolium alexandrinum L. aqueous extract (TAAE), along with two isolated compounds, caffeine (CAF) and saponin (SAP), in a rat model of acute gouty arthritis (GA). MATERIALS AND METHODS: The GA model was established by injecting a monosodium urate (MSU) suspension into the knee joint. Synovial tissue pathology was assessed, and levels of TNF-α, IL-6, IL-1ß, NF-κB, mTOR, AKT1, PI3K, NLRP3, and ASC were measured by ELISA. mRNA expression of ERK1, JNK, and p-38 MAPK was detected using qRT-PCR, and Caspase-1 protein expression was assessed by immunohistochemical analysis. Knee swelling, uric acid levels, liver and kidney function, and oxidative stress markers were also evaluated. RESULTS: TAAE analysis identified 170 compounds, with 73 successfully identified using LC-HR-MS/MS, including caffeine citrate and theasapogenol B glycoside as the main constituents. The studied materials demonstrated significant protective effects against GA. TR25 administration significantly mitigated knee joint circumference compared to other treatments. It demonstrated potential in alleviating hyperuricemia, renal and hepatic impairments induced by MSU crystals. TR25 also alleviated oxidative stress and reduced levels of IL1ß, IL-6, TNF-α, and NF-κB. Weak Caspase-1 immune-positive staining was observed in the TR25 group. TR25 decreased NLRP3 and ASC expression, reducing inflammatory cytokine levels in GA. It effectively inhibited the PI3K, AKT, and mTOR signaling pathways, promoting autophagy. Additionally, TR25 suppressed ERK1, JNK, and p-38 MAPK gene expression in synovial tissue. These effects were attributed to various components in TAAE, such as flavonoids, phenolic acids, tannins, alkaloids, and triterpenes. CONCLUSION: Importantly, irradiation (25 KGy) enhanced the antioxidant effects and phtchemical contents of TAAE. Additionally, TR0, TR25, CAF, and SAP exhibited promising protective effects against GA, suggesting their therapeutic potential for managing this condition. These effects were likely mediated through modulation of the NLRP3/ASC/Caspase-1 and ERK/JNK/p-38 MAPK signaling pathways, as well as regulation of the PI3K/AKT/mTOR pathway. Further research is warranted to fully elucidate the underlying mechanisms and optimize their clinical applications.

4.
Health Psychol Behav Med ; 12(1): 2377716, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39010867

RESUMEN

Background: As the recognition of psychological factors in chronic illness management grows, this study examined the interplay of psychological traits - grit, self-efficacy, resilience, and nature-relatedness - and their collective impact on the Quality of Life (QoL) among patients with rheumatoid arthritis (RA) in Malaysia. Methods: A cross-sectional study was conducted among 222 patients with RA at a private hospital in Malaysia. Utilizing validated scales, including the Connor-Davidson Resilience Scale, Short Grit Scale, Nature Relatedness Scale, and Arthritis Self Efficacy Scale, data were collected. Pearson Product-moment Correlation analyses assessed the relationships between variables, and a multiple mediation analysis explored the mediating effects of resilience, grit, and self-efficacy on the relationship between nature-relatedness and QoL. Findings: Of the 222 participants (86% female, mean age = 56.03, S.D. = 13.42), the analysis revealed a significant mediating role of resilience in the relationship between nature-relatedness and QoL among RA patients (b = -.117, SE = .042, 95% BCa CI [-.208, -.046]). Although grit and self-efficacy positively correlated with QoL, they did not serve as significant mediators in the nature-relatedness - QoL relationship. This highlights the pivotal role of building a sense of resiliency among patients with RA. Interpretation: Individuals with RA are not only resilient in terms of their psychological traits such as grit, self-efficacy, and general resilience but also exhibit resilience in their connection and interaction with the natural environment (nature-relatedness). This holistic concept recognizes that fostering resilience in both psychological aspects and the context of one's environment is crucial for promoting overall well-being, particularly in the management of chronic illnesses like RA. It emphasizes the interconnectedness of psychological factors and environmental engagement in contributing to an individual's ability to cope and thrive despite health challenges.

5.
Caspian J Intern Med ; 15(3): 542-545, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011429

RESUMEN

Background: Salmonella osteoarticular involvement is a rare complication, occurring in about 2% of the cases. Septic arthritis is exceedingly rare, involving only 0.2 % of all salmonellosis patients. Endocarditis is another complication that occurs in less than 0.8 % of cases. These complications are more likely to happen among immunocompromised patients. Case Presentation: We report a previously healthy 25-year-old man who presented with left limb pain. He had been treated for brucellosis ten days earlier by his primary care physician. Arthrocentesis and subsequent hip-joint biopsy confirmed septic arthritis due to Salmonella. However, he was unresponsive to the treatment. We found no underlying immunosuppression. A trans-esophageal echo was performed due to the continued fever and positive blood cultures. It revealed Salmonella endocarditis of the naïve tricuspid valve. He was treated via arthrotomy and antimicrobials for four weeks. Follow-up after 20 months showed no underlying immunosuppression. Conclusion: This case highlights that in patients with positive Salmonella blood cultures and a focus of infection compatible with Salmonellosis but unresponsive to treatment, searching for other foci of infection is necessary. Furthermore, physicians in endemic areas of brucellosis should consider other differential diagnoses in patients with fever and limping because any delay in diagnosing Salmonella septic arthritis can destroy the joint space with lifelong discomfort.

6.
Rheumatol Ther ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39017907

RESUMEN

INTRODUCTION: Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy. METHODS: Patients aged ≥ 18 years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1 bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates. RESULTS: A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs [95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. In the All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36 (0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59). CONCLUSIONS: The use of bDMARDs was not a time-dependent risk factor for malignancy.

8.
Chem Biol Drug Des ; 104(1): e14582, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39013795

RESUMEN

Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti-citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B-lineage cells by preventing BCR activation, FC-receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune-mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.


Asunto(s)
Agammaglobulinemia Tirosina Quinasa , Artritis Reumatoide , Inhibidores de Proteínas Quinasas , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Humanos , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Agammaglobulinemia Tirosina Quinasa/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Animales , Linfocitos B/metabolismo , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos B/metabolismo , Transducción de Señal/efectos de los fármacos
9.
Immunopharmacol Immunotoxicol ; : 1-12, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39013842

RESUMEN

OBJECTIVE: Rheumatoid arthritis (RA), a chronic inflammatory disease, is characterized by joint swelling, cartilage erosion, and bone destruction. This study investigated the therapeutic efficacy of Carnosic acid (CA), a natural compound with anti-inflammatory and antioxidant properties, in an adjuvant-induced arthritis model. METHODS: Paw swelling and arthritis index were measured. Oxidative stress markers, including lipid peroxidation and antioxidant enzyme levels, were assessed. Synovial tissue was analyzed for pro-inflammatory markers using real-time Q-PCR and Western blotting. The expression of mPGES-1 was determined by Western blotting. Peripheral neuropathic pain was assessed using cold and mechanical allodynia tests. Bone loss was quantitatively assessed through microcomputed tomography (µCT) scanning of femurs and X-ray radiography. Indomethacin-induced gastric ulcers were evaluated. Molecular docking studies were conducted to analyze the binding affinity of CA to mPGES-1. RESULTS: The CA treatment not only demonstrated a significant reduction in joint inflammation and paw swelling but also mitigated oxidative stress and improved the antioxidant defence system. CA inhibited microsomal prostaglandin E synthase-1 (mPGES-1) expression and the expression of pro-inflammatory molecules such as inducible nitric oxide synthase (iNOS) and cyclooxygenases-2 (COX-2), thus attenuating the arthritis symptoms without severe gastrointestinal side effects. Additionally, it inhibited the expression of pro-inflammatory molecules such as iNOS and COX-2, contributing to the reduction of arthritis symptoms. Notably, CA treatment prevented the common side effects of traditional RA treatments like corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), including weight loss, bone degradation, and gastric ulcers. CONCLUSIONS: These findings suggest that CA, through specific enzyme inhibition, offers a compelling alternative therapeutic approach for RA. Further research is warranted to explore the potential of CA in other arthritis models and its suitability for human RA treatment.


CA significantly reduces inflammation in FCA induced arthritis model.CA treatment inhibits key pro-inflammatory molecules, including mPGES-1 and COX-2In silico docking studies confirm the affinity of CA to mPGES-1.CA prevents bone loss and avoids side effects seen with standard treatments.Antioxidant properties of CA counteract oxidative stress related to chronic inflammation.

10.
J Acad Nutr Diet ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025233

RESUMEN

BACKGROUND: Various foods and nutrients are linked with higher or lower risk of rheumatoid arthritis (RA), yet these associations are inconsistent across studies. Limited research has been done evaluating the association between diet quality and RA in a larger scale prospective study on postmenopausal women. OBJECTIVE: The objective of this study was to evaluate the association between dietary quality and risk of incident RA in postmenopausal women. DESIGN: This is a prospective cohort study as part of the Women's Health Initiative (WHI) with an average follow-up time of 8.1 years. Baseline diet was measured using a food frequency questionnaire (FFQ). Diet quality was evaluated by the Healthy Eating Index (HEI) - 2015 total score. In addition, intake of food groups/nutrients that align with HEI-2015 components was assessed. PARTICIPANTS/SETTING: 109,591 postmenopausal women were included in this study, which was conducted at various clinical centers across the US with recruitment from 1993 to 1998. WHI participants who were missing outcome data, had unreliable/missing FFQ data, or had RA at baseline were excluded. MAIN OUTCOME MEASURES: The primary outcome measure is incident RA. STATISTICAL ANALYSES PERFORMED: Multivariable Cox proportional regression analysis was performed evaluating the association of diet quality with self-reported physician-diagnosed RA after adjusting for age, race, ethnicity, education status, income, and body mass index (BMI). RESULTS: During 857,517 person-years of follow-up, 5,823 incident RA cases were identified. After adjustment for multiple comparisons, compared to quartile 1, quartiles 2, 3, and 4 of the HEI-2015 total scores were associated with a lower RA risk of 1%, 10%, and 19%, respectively (p-trend < 0.001). Greater consumption of total fruits (p-trend=0.014), whole fruits (p-trend<0.0002), total vegetables (p-trend=0.008), greens and beans (p-trend<0.0002), whole grains (p-trend=0.008), and dairy (p-trend=0.018) were significantly associated with lower rates of incident RA. Conversely, higher consumption of saturated fat (p-trend=0.002) was significantly associated with higher rates of incident RA. CONCLUSION: A higher quality diet reflected by higher HEI-2015 total scores was inversely associated with incident rheumatoid arthritis in post-menopausal women.

11.
Biochim Biophys Acta Mol Basis Dis ; : 167341, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39025373

RESUMEN

Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m6A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m6A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m6A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m6A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.

12.
Rev Mal Respir ; 2024 Jul 17.
Artículo en Francés | MEDLINE | ID: mdl-39025770

RESUMEN

INTRODUCTION: Methotrexate (MTX) is a folate antagonist used as an immunosuppressant in a number of conditions, including rheumatoid arthritis (RA). Low-dose MTX (MTX-LD) is associated with a risk of haematological, hepatic, gastrointestinal and pulmonary toxicity, which may up until now have limited its use. STATE OF THE ART: In RA, data from retrospective cohorts have reported a possible excess risk of methotrexate toxicity in cases of underlying interstitial lung disease (ILD). However, recent prospective and retrospective multicentre studies have found no such increased risk, and have reassuringly concluded that MTX-LD can be prescribed in cases of RA-associated ILD (RA-ILD). PERSPECTIVES AND CONCLUSIONS: Current recommendations are not to delay the introduction of MTX in patients with RA at risk of developing ILD or in the presence of RA-ILD with mild to moderate respiratory impairment.

13.
Front Immunol ; 15: 1399249, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015574

RESUMEN

Reactive arthritis(ReA), a form of arthritis occurring post-infection, manifests with antecedent infection symptoms, arthritis, and extra-articular manifestations, categorizing it as spondyloarthritis. "Keratoderma blennorrhagicum" (characterized by pustular hyperkeratosis on palms and soles, resembling pustular psoriasis) represents the most typical skin manifestation of ReA, occurring in acute or chronic phases. Severe lesions necessitate systemic disease modifying anti-rheumatic drugs (DMARDs) or biologic therapies. This article reports a case of ReA with sacroiliitis and widespread pustular eruptions following a urinary tract infection. Treatment with sulfasalazine and thalidomide significantly improved sacroiliitis, but the skin rash remained persistent and recurring. Subsequent use of adalimumab and secukinumab resulted in worsening skin rash, prompting a switch to tofacitinib, leading to a remarkable improvement in pustular eruptions after 20 days of treatment. This case demonstrates successful application of tofacitinib in treating severe keratoderma blennorrhagicum refractory to conventional DMARDs and biologics, offering insights into JAK inhibition for challenging rheumatic diseases with skin involvement.


Asunto(s)
Artritis Reactiva , Piperidinas , Pirimidinas , Humanos , Piperidinas/uso terapéutico , Pirimidinas/uso terapéutico , Artritis Reactiva/tratamiento farmacológico , Artritis Reactiva/etiología , Masculino , Femenino , Adulto , Resultado del Tratamiento , Antirreumáticos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico
14.
Rheumatol Immunol Res ; 5(2): 126-129, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39015846

RESUMEN

Background and Objectives: The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. Methods: A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Results: Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Conclusions: Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

15.
Mol Divers ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970640

RESUMEN

Rheumatoid Arthritis (RA) is a chronic, symmetrical inflammatory autoimmune disorder characterized by painful, swollen synovitis and joint erosions, which can cause damage to bone and cartilage and be associated with progressive disability. Despite expanded treatment options, some patients still experience inadequate response or intolerable adverse effects. Consequently, the treatment options for RA remain quite limited. The enzyme AKT1 is crucial in designing drugs for various human diseases, supporting cellular functions like proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. Therefore, AKT serine/threonine kinase 1 is considered crucial for targeting therapeutic strategies aimed at mitigating RA mechanisms. In this context, directing efforts toward AKT1 represents an innovative approach to developing new anti-arthritis medications. The primary objective of this research is to prioritize AKT1 inhibitors using computational techniques such as molecular modeling and dynamics simulation (MDS) and shape-based virtual screening (SBVS). A combined SBVS approach was employed to predict potent inhibitors against AKT1 by screening a pool of compounds sourced from the ChemDiv and IMPPAT databases. From the SBVS results, only the top three compounds, ChemDiv_7266, ChemDiv_2796, and ChemDiv_9468, were subjected to stability analysis based on their high binding affinity and favorable ADME/Tox properties. The SBVS findings have revealed that critical residues, including Glu17, Gly37, Glu85, and Arg273, significantly contribute to the successful binding of the highest-ranked lead compounds at the active site of AKT1. This insight helps to understand the specific binding mechanism of these leads in inhibiting RA, facilitating the rational design of more effective therapeutic agents.

16.
Hum Immunol ; 85(5): 110838, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970880

RESUMEN

BACKGROUND: T follicular helper (Tfh) cells are a subdivision of T helper cells involved in antigen-specific B cell immunity. Tfh cells play an essential role in the interaction of T cells/B cells in the germinal centers (GC), and dysregulation of Tfh actions can offer pathogenic autoantibody formation and lead to the development of autoimmune diseases. This study seeks to evaluate changes in Tfh frequency and its related cytokines in autoimmune disease, its association with disease phase, severity, prognosis, and the effect of immunosuppressive treatment on the Tfh population. METHOD: The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. Electronic databases, including PubMed, Scopus, Web of Science, and Embase, were systematically searched for potentially eligible studies up to January 1, 2024. RESULTS: We identified 4998 articles in the initial search, from which 1686 similar titles were removed. A total of 3312 articles were initially screened, and 3051 articles were excluded by title/abstract screening. A total of 261 studies were considered for full-text assessment, and 205 articles were excluded by reason. Finally, a total of 56 studies were included in our review. CONCLUSION: The population of Tfh cells is generally higher in autoimmune diseases versus Health control. Moreover, the number of Tfh cells is associated with the disease severity and can be considered for determining the prognosis of studies. Also, peripheral blood circulating Tfh (cTfh) cells are an available sample that can be used as an indicator for diagnosing diseases.

17.
Semin Arthritis Rheum ; 68: 152498, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38970896

RESUMEN

OBJECTIVE: This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis. METHODS: Two researchers conducted a comprehensive search of Chinese and English databases from their inception until July 2023. The literature screening and data extraction were then performed. Statistical analysis was carried out using RevMan 5.4 software. RESULTS: A total of 36 relevant RCTs, involving 2,076 participants, were ultimately included in this study. These RCTs encompassed four types of inflammatory arthritis, namely rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis (AS), and systemic sclerosis (SSc). The results demonstrated that MSC therapy exhibited improvements in the Visual Analog Scale (VAS) for pain in OA patients (bone marrow: SMD=-0.95, 95 % CI: -1.55 to -0.36, P = 0.002; umbilical cord: SMD=-2.03, 95 % CI: -2.99 to -1.07, P < 0.0001; adipose tissue: SMD=-1.26, 95 % CI: -1.99 to -0.52, P = 0.0009). Specifically, MSCs sourced from adipose tissue showed enhancements in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (P = 0.0001), WOMAC physical function (P = 0.001), and total WOMAC scores (P = 0.0003). As for MSC therapy in RA, AS, and SSc, the current systematic review suggests a potential therapeutic effect of MSCs on these inflammatory arthritic conditions. Safety assessments indicated that MSC therapy did not increase the incidence of adverse events. CONCLUSION: MSCs have the potential to alleviate joint pain and improve joint function in patients with inflammatory arthritis. Moreover, MSC therapy appears to be relatively safe and could be considered as a viable alternative treatment option for inflammatory arthritis.

18.
Gait Posture ; 113: 272-279, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38970929

RESUMEN

BACKGROUND: Total ankle arthroplasty (TAA) is used to treat symptomatic end-stage ankle arthritis (AA). However, little is known about TAA's effects on gait symmetry. RESEARCH QUESTION: Determine if symmetry changes from before surgery through two years following TAA utilizing the normalized symmetry index (NSI) and statistical parametric mapping (SPM). METHODS: 141 patients with end-stage unilateral AA were evaluated from a previously collected prospective database, where each participant was tested within two weeks of surgery (Pre-Op), one year and two years following TAA. Walking speed, hip extension angle and moment, hip flexion angle, ankle plantarflexion angle and moment, ankle dorsiflexion angle, weight acceptance (GRF1), and propulsive (GRF2) vertical ground reaction forces were calculated for each limb. Gait symmetry was assessed using the NSI. A linear mixed effects model with a single response for each gait symmetry variable was used to examine the fixed effect of follow-up time (Pre-Op, Post-1 yr, Post-2 yr) and the random effect of participant with gait speed as a covariate in the model. A one-dimensional repeated measures analysis of variance (ANOVA) statistical parameter mapping (SPM) was completed to examine differences in the time-series NSI to determine regions of significant differences between follow-up times. RESULTS: Relative to Pre-Op values, GRF1, and GRF2 showed increased symmetry for discrete metrics and the time-series NSI across sessions. Hip extension moment had the largest symmetry improvement. Ankle plantarflexion angle was different between Pre-Op and Post-2 yr (p=0.010); and plantarflexion moment was different between Pre- Op and each post-operative session (p<0.001). The time-series Ankle Angle NSI was greater during the early stance phase in the Pre-Op session compared to Post-2 yr. SIGNIFICANCE: Symmetry across most of the stance phase improved following TAA indicating that TAA successfully improves gait symmetry and future work should determine if these improvements restore symmetry to levels equivalent with health age-match controls.

19.
Injury ; 55(8): 111704, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38970924

RESUMEN

INTRODUCTION: Alteration of sagittal alignment during fracture fixation directly impacts ankle motion in dorsiflexion and plantarflexion. Previously research measured the anterior distal tibia angle (ADTA) in a normal healthy population. The null hypothesis for this study is that ADTA is restored to normal range following unstable pilon fractures. The aim of this study is to identify the range of the ADTA in distal tibia fractures after surgical fixation, compared to a previously published normal population. MATERIAL AND METHODS: A retrospective review of operative distal tibia fractures (AO/OTA classification 43A and 43C - 43B were excluded due to lower likelihood of fracture changing the ADTA) was performed. ADTA on lateral radiograph was measured as the angle relative to the tibia shaft. RESULTS: 100 patients with post-operative radiographs that met inclusion criteria were analyzed. The average ADTA was 6.9° (⌠=4.62°) with a maximum slope of 19.2° (i.e. anterior orientation) and a minimum of -3.3° (i.e. posterior orientation). The uninjured population had an average ADTA of 6.0° (range -2.0°-14°, ⌠=3.0°). CONCLUSION: This analysis shows the average distal tibia sagittal alignment in the post-surgical group is similar to a normal, uninjured population. Large alterations in ADTA would directly impact the ankle in the plane of motion (i.e. negative ADTA would decrease ankle dorsiflexion). Considering ADTA as an objective intra-operative parameter optimizes sagittal plane alignment.

20.
Int J Surg Case Rep ; 121: 110004, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38971035

RESUMEN

INTRODUCTION AND IMPORTANCE: Epidural abscess is a rare but serious infection. Although more commonly seen in men over 50, our case is notable for its occurrence in a pediatric patient, highlighting the unusual nature of this abscess at such a young age, particularly in conjunction with septic arthritis of the hip. CASE PRESENTATION: A 10-year-old child was admitted to pediatrics for investigation of a prolonged fever. The child presented with back pain associated with left hip lameness. An MRI of the spine showed an epidural collection extending from the 4th to the 10th dorsal vertebrae. This collection compressed the spinal cord. An MRI of the left hip showed an appearance consistent with septic arthritis. A left hip arthrotomy was performed, with laminectomy and drainage of the epidural abscess at D7. The patient was treated with antibiotics. The clinical and biological evolution was favorable. CLINICAL DISCUSSION: Epidural abscess is a rare but serious infection, now more easily diagnosed by MRI. It is most often caused by hematogenous spread, mainly by Staphylococcus aureus. Symptoms include back pain, neurological signs and fever. Diagnosis is confirmed by MRI. Early diagnosis is essential to prevent neurological complications and death, as the disease can progress to paralysis. Treatment consists of intravenous antibiotics and surgical intervention as indicated. CONCLUSION: Early diagnosis of spinal epidural abscess is important to prevent neurological complications, sepsis and even death. It should be noted that there are no official recommendations or guidelines for the management of epidural spinal abscesses in the pediatric population.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA